miR604A>G gene polymorphism is associated with recurrent pregnancy loss in Turkish women

SUMMARY OBJECTIVE: Recurrent pregnancy loss is considerably a reproductive health problem for couples. Genetic, epigenetic, and environmental factors play an important role in the development of recurrent pregnancy loss. While there are many causes, genetic and epigenetic factors are common. In this study, we aimed to examine the association between miR604 (rs2368393) A>G gene polymorphism and the risk of recurrent miscarriage in the Turkish population. METHODS: The study included 250 participants (i.e., 150 patients and 100 controls). DNA samples were isolated from peripheral blood, and polymerase chain reactions and restriction fragment length polymorphism methodologies were applied. RESULTS: The genotype distribution and allele frequencies of miR604A>G gene showed statistically significant differences between patients and control groups (p=0.002 and p<0.002, respectively). CONCLUSION: As a result of the study, we found that the AA genotype and A allele of the miR604A>G gene were statistically significant for the risk of recurrent pregnancy loss in Turkish women.

Correlation of anti-phosphatidylserine/prothrombin antibodies with unexplained recurrent miscarriages / 北京大学学报(医学版)

OBJECTIVE@#To investigate whether anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes were correlated with unexplained recurrent miscarriages.@*METHODS@#In our a single-center retrospective study, 283 patients with at least one unexplained miscarriage who visited the Third Hospital of Peking University between January 2021 and August 2023, aged between 18-40 years, and tested for anti-phosphatidylserine/prothrombin antibodies IgG or IgM subtypes, were included. The patients with either positive IgG or IgM anti-phosphatidylserine/prothrombin antibody were regarded as positive for anti-phosphatidylserine/prothrombin antibody. SPSS 26.0 software was used for statistical analysis. Chi-square test and Logistic regression analysis were used to study the correlation of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes with unexplained recurrent miscarriages. And the diagnostic sensitivity, specificity, the positive predictive value, the negative predictive value of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes in unexplained miscarriages was calculated with four-fold table.@*RESULTS@#Chi-square analysis showed that anti-phosphatidylserine/prothrombin antibodies and its IgM subtypes were correlated with recurrent miscarriages (both P < 0.05), while the IgG subtype was not correlated with recurrent miscarriages (P>0.05). After adjusting with anticardiolipin antibodies, anti-β2 glycoprotein antibodies, lupus anticoagulants, antinuclear antibodies, and age by Logistic regression analysis, anti-phosphatidylserine/prothrombin antibodies were correlated with unexplained recurrent miscarriages (OR=2.084, 95%CI 1.045-4.155, P < 0.05), and anti-phosphatidylserine/prothrombin antibody IgM subtypes were correlated with unexplained recurrent miscarriages (OR=2.368, 95%CI 1.187-4.722, P < 0.05).The sensitivity of anti-phosphatidylserine/prothrombin antibody in recurrent miscarriage was 65.43%, the specificity was 48.51%, the positive predictive value was 33.76%, and the negative predictive value was 77.78%. In the patients with recurrent miscarriages with negative classical antiphospholipid antibodies, the sensitivity of anti-phosphatidylserine/prothrombin antibody was 59.09%, the specificity was 63.23%, the positive predictive value was 40.63%, and the negative predictive value was 78.40%. The sensitivity of the anti-phosphatidylserine/prothrombin antibody IgM subtype for the diagnosis of recurrent miscarriage was 65.43%, the specificity was 50.99%, the positive predictive value was 34.87%, and the negative predictive value was 78.63%.@*CONCLUSION@#Anti-phosphatidylserine/prothrombin antibody and IgM subtype antibody are correlated with unexplained recurrent miscarriages in patients with at least one unexplained miscarriage. Whether positive anti-phosphatidylserine/prothrombin antibody or IgM subtype could predict future unexplained recurrent miscarriages warrants a prospective study.

Effectiveness of low-molecular-weight heparin in obstetric outcome of pregnancies having comorbidities with potential thrombotic risk

Background: The term “miscarriage” represents a demise of a fetus before it attains maturity. It encompasses all miscarriages between the time of conceive and the end of the pregnancy. Antiphospholipid antibody syndrome and in vitro fertilization (IVF) are one of the major reasons for thrombosis in pregnancy causing miscarriages. Since low-molecular-weight heparin (LMWH) produces fewer thrombocytopenia and is associated with reduced incidence of osteoporosis, it can be given once daily, therefore, it might have significant benefits compared with unfractionated heparin in at risk pregnancy. Aims and Objectives: This study aims to assess pregnancy outcomes after therapy with traditional aspirin supplemented with LMWH among women who are pregnant experiencing thrombosis-related diseases such as antiphospholipid syndrome (APLA) syndrome and IVF pregnancies. Materials and Methods: It was a retrospective analysis with a purposive sample of 61 pregnant women who had thrombosis risk factors. Thirty of the pregnancies were confirmed cases for APLA syndrome, whereas the other 30 were IVF conceptions. The comorbid factors were older age, a past of miscarriages, nulliparous IVF pregnancy, pre-eclampsia, diabetes, and obesity. IVF pregnancy accompanied with ovarian hyperstimulation syndrome was one of the cases. Study participants were administered a regular preventive medication of 40/60 mg s.c. as well as 75/150 mg of oral aspirin. All through gestation, according to patient’s registration weight, were administered every day. Heparin was stopped 24 h before the actual scheduled delivery, while aspirin had been stopped 3–4 days earlier. Results: In this study, 58 live births have been recorded, including 10 cases of preeclampsia, 10 of intrauterine growth retardation, two of eclampsia, two of intrauterine death infants, and two of abortions. There were 18 premature deliveries, nine multiple birth pregnancies, and 35 full-term pregnancies among the live births. There were no cases of HELLP syndrome, placental abruption, and stillbirths. In addition, heparin therapy cured one incidence of post-operative thrombosis of deep veins in pregnancy. It was also observed that early LMWH application to pregnant women with thrombosis risk was able to lower the incidence of miscarriages, gestational fetal death, and decreased weight at birth, and cases of HELLP syndromes. Furthermore, the therapeutic dose in high-risk case of post-delivery deep vein thrombosis of lower extremities cured the mother. Conclusion: It can be concluded from the study that the application of LMWH enhanced the obstetric outcome in pregnant women having increased risk for thrombosis. In future pregnancies with thrombosis risk factors, employing LMWH in conjunction with the documented therapeutic approach may result in a better obstetric outcome.

Tratamiento quirúrgico conservador del embarazo intersticial, con antecedente de salpingectomía homolateral. Reporte de un caso / Conservative surgical management of interstitial pregnancy, with a history of ipsilateral salpingectomy. Report of a case

Resumen ANTECEDENTES: El procedimiento quirúrgico del embarazo intersticial puede complicarse con hemorragia difícil de controlar; por esto en los últimos años se recurre a las técnicas que permiten el control hemostático, con lo que disminuyen la morbilidad y mortalidad relacionadas con el procedimiento. OBJETIVO: Describir el proceso para establecer el diagnóstico y decidir el tratamiento quirúrgico conservador en una paciente con embarazo intersticial con antecedente de salpingectomía homolateral y deseo de preservación uterina. CASO CLINICO: Paciente de 27 años, con antecedentes de un parto, tres abortos y un embarazo ectópico previo, con salpingectomía izquierda. Acudió a consulta debido a un retraso menstrual de siete semanas y dolor pélvico agudo. Ante la sospecha de embarazo ectópico se integró el protocolo diagnóstico. La cuantificación de la fracción-β de hormona gonadotropina coriónica fue de 8962 mlU/mL, el ultrasonido transvaginal reportó una imagen compatible con saco gestacional hacia la región del cuerno izquierdo y probable hemoperitoneo. En la laparotomía exploradora se encontraron: hemoperitoneo y embarazo intersticial izquierdo. Con el propósito de preservar la fertilidad se hizo una doble ligadura de la arteria uterina izquierda, a nivel de istmo uterino y del ligamento útero-ovárico y resección del saco gestacional intersticial, con cornuostomía. CONCLUSION: El embarazo intersticial es una urgencia obstétrica con alto riesgo de ruptura y hemorragia, por fortuna poco frecuente. La ligadura de las arterias uterinas, previa a la ablación quirúrgica del saco gestacional, es una alternativa individualizada en pacientes con esta complicación.

Abstract BACKGROUND: The surgical procedure of interstitial pregnancy can be complicated by bleeding that is difficult to control; for this reason, in recent years, techniques that allow hemostatic control to have been used, thus reducing morbidity and mortality related to the procedure. OBJECTIVE: To describe the process to establish the diagnosis and decide the conservative surgical treatment in a patient with interstitial pregnancy with a history of homolateral salpingectomy and desire for uterine preservation. CLINICAL CASE: 27-year-old patient, with a history of one childbirth, three miscarriages and a previous ectopic pregnancy, with left salpingectomy. She came for consultation due to a seven-week menstrual delay and acute pelvic pain. In view of the suspicion of ectopic pregnancy, the diagnostic protocol was integrated. The quantification of the β-fraction of chorionic gonadotropin hormone was 8962 mlU/mL, the transvaginal ultrasound reported an image compatible with gestational sac towards the left horn region and probable hemoperitoneum. At exploratory laparotomy, hemoperitoneum and left interstitial pregnancy were found. To preserve fertility, a double ligation of the left uterine artery at the level of the uterine isthmus and the utero-ovarian ligament and resection of the interstitial gestational sac with cornuostomy was performed. CONCLUSION: Interstitial pregnancy is an obstetric emergency with a high risk of rupture and hemorrhage, fortunately rare. Ligation of the uterine arteries, prior to surgical ablation of the gestational sac, is an individualized alternative in patients with this complication.

Covid 19, the Kerala experience: an observational, single centre retrospective study of outcome in covid positive pregnancies

Background: Covid 19 has spread across the world at an alarming rate. Approximately 4.05 million people have got infected worldwide resulting in around 279,000 deaths. Over 1 million people have recovered worldwide. Aim of this study was to determine whether course and severity of covid 19 is altered in pregnant women and whether covid 19 seemed to worsen the prognosis in pregnant women.Methods: Around 50 covid positive patients were admitted to this study hospital, a tertiary care referral hospital and medical college, between march and May 2020, 11 were pregnant. Authors collected their data retrospectively to understand the course of their disease till the period of recovery.Results: There were 6 patients above 31 weeks of whom one had elective repeat caesarean section, one had full term vaginal delivery, one is under follow up. Three patients had foetal distress necessitating emergency caesarean section. Of the remaining 5 patients with periods of gestation between 9-13 weeks, 1 of 24 weeks, 6 patients above 31 weeks, one had a miscarriage. Rest pregnancies are continuing and under follow up. 6 women had been symptomatic at admission, with mild symptoms of low-grade fever, sore throat and rhinitis. All were treated with hydroxychloroquine (HCQs). Those with respiratory symptoms like cough were also treated with oseltamivir. In view of high prevalence of H1N1 in the region. None of the women developed severe disease. The disease did not appear to worsen prognosis in pregnant women. The rate of recovery in pregnant women was similar to that seen in non-pregnant women and also men under the age of 40 years admitted in this study hospital.Conclusions: Covid 19 did not seem to worsen the prognosis in pregnant individuals when compared to rest of the population. The foetal outcomes also seemed favorable. However larger studies are required before concrete guidelines could be formulated for management of the disease in pregnancy.

Chronic histiocytic intervillositis in consecutive miscarriages: A potential pitfall in routine examination of conceptus

@#Introduction: Chronic histiocytic intervillositis (CHI) is a rare placental lesion strongly associated with recurrent miscarriages and fetal losses. It requires histopathological diagnosis and can only be made after delivery of the products of conception (POC). We describe a case of CHI in a 41-yearold lady with a 16-year history of thirteen recurrent consecutive first trimester miscarriages. Case report: The patient is a 41-year-old lady who suffered first trimester miscarriages in all her thirteen pregnancies. The relevant clinical investigations revealed neither significant nor helpful findings in determining the cause of recurrent miscarriages. Histological findings in each except one of the submitted conceptual tissue showed similar features of histiocytic aggregates primarily within the intervillous spaces, a characteristic description of CHI. One of the samples showed degenerative changes. Discussion: Practicing pathologists are not familiar with the histological features of CHI and this may be a potential pitfall in routine examination of POCs. Recognising this entity allows for accurate diagnosis and hence better management. The aetiology remains unclear, although an immunopathological basis are being explored.

Occurrence of hypothyroidism and its correlation with reproductive health problems: a cross sectional study

Background: Thyroid dysfunction is 10 times more common in women than in men. Hypothyroidism among women of reproductive age group is linked to menstrual irregularities, polycystic ovarian syndrome (PCOS), miscarriage and infertility. Several studies are available in the literature reporting regarding impact of hypothyroidism on one or the other isolated problems of reproductive health problems.Methods: This cross-sectional study is conducted including 290 participants having various reproductive health problems attending the gynaecology OPD of a rural based tertiary care hospital of Tamil Nadu during the year 2017-2018.These participants were investigated for thyroid dysfunction and its correlation of hypothyroidism with reproductive health problems viz. menstrual irregularities, Polycystic ovarian diseases (PCOS), infertility and pregnancy loss was studied.Results: It was observed that 80.6% of the 290 participants were euthyroid and 16.97% were hypothyroid, who presented with menstrual irregularities like menorrhagia (28.6%), oligomenorrhea (20.8%), amenorrhoea (21.3%), PCOS (28.6%), infertility (21.6%) and 23.8% hypothyroid women had pregnancy losses of varying number.Conclusions: In present study the occurrence of hypothyroidism was found to be 16.89%. Since hypothyroidism has close association with problems like menstrual irregularities, PCOS, miscarriages and infertility, thyroid function test should be routinely recommended for these women. Thyroid dysfunction can be corrected with simple, cost-effective treatment.  This will help in improvement in pregnancy outcome and also avoid subjecting women for major surgeries for menorrhagia.

Alterações genéticas em casais com antecedentes de aborto recorrente no primeiro trimestre da gestação / Genetic alterations in couples with a history of recurrent miscarriage in the first trimester of pregnancy

O abortamento é considerado um problema multifatorial, cujas principais causas envolvidas na sua etiologia são os fatores ambientais (como exposição a substâncias tóxicas), genéticos, anatômicos, endócrinos, imunológicos, trombofílicos e doenças infecciosas (como toxoplasmose, rubéola). No entanto, os fatores genéticos são atribuídos principalmente aos abortamentos de primeiro trimestre da gestação. As alterações cromossômicas, o polimorfismo C677T, no gene da metilenotetrahidrofolato redutase (MTHFR677C>T); o polimorfismo G1691A, no gene do Fator V de Leiden (FVL1691G>A), e o polimorfismo G20210A, no gene da protrombina (PRT20210G>A), têm sido associados a problemas obstétricos, incluindo aborto recorrente. O objetivo deste trabalho foi investigar associação entre as mutações relacionadas à trombofilia, presença de alterações cromossômican e a ocorrência de aborto espontâneo recorrente e avaliar possíveis interações entre as referidas mutações e as alterações cromossômicas. A casuística foi composta por 151 mulheres com história de aborto recorrente, 94 parceiros e 100 controles (mulheres sem histórico de aborto). A investigação das mutações foi realizada pela técnica de Reação em Cadeia da Polimerase- Polimorfismo de Tamanho de Fragmento de Restrição. As alterações cromossômicas foram investigadas pela cariotipagem com banda–G. A frequência das alterações cromossômicas foi de 7,3% nas mulheres com abortamento recorrente e 1% nos controles (p=0,022), e de 2,1% nos parceiros. No entanto, a frequência dos alelos MTHR677C>T (23% versus 22,5%), FVL1691G>A (1,5% versus 1% ) e PRT20210G>A (1,45% versus 0%) foi similar entre casos e controles, respectivamente. No grupo investigado, foi observada associação entre aborto recorrente e alterações cromossômicas, mas não foi encontrada associação com os polimorfismos gênicos investigados.

Abortion is considered a multifactorial problem, the most important causes involved in its etiology are, environmental factors ( as exposure to toxic chemicals), genetic, anatomic, endocrine, immunological, thrombophilic and infectious diseases (such as toxoplasmosis, rubella). However, genetic factors are mainly attributed to abortions of the first trimester of pregnancy. Chromosomal abnormalities, MTHFR 677C>T, factor V Leiden 1691G>A and prothrombin 20210G>A mutations have been associated with obstetric problems, including recurrent miscarriage. The objective of this research was to investigate associations between mutations in three genes commonly associated to thrombophilic events, chromosomal abnormalities and the occurrence of recurrent miscarriage. As well evaluate possible interactions between these mutations and chromosomal abnormalities. The sample was comprised of 151 women with history of recurrent miscarriages, 94 partners and 100 control (women with no history of abortion). The investigation of the mutations was performed by Polymerase Chain Reaction (PCR)/ Restriction Fragment Length Polymorphism (RFLP). Chromosomal aberrations were investigated by karyotyping with G-banda. The frequency of chromosomal abnormalities was 7.3% in women with recurrent miscarriage and 1% in controls (p = 0.022), and 2.1% in the partners. However, the frequency of allele MTHR677C> T (23% versus 22.5%), FVL1691G> A (1.5% vs. 1%) and PRT20210G> A (1.45% vs. 0%) was similar for cases and controls, respectively. In the investigated group was found association between recurrent miscarriage and chromosomal abnormalities, but no association was found with the genetic polymorphisms investigated.

Genetic counseling in carriers of reciprocal translocations involving two autosomes.

One of the main genetic causes involve in the pathogenesis of recurrent abortion is parental chromosomal abnormalities. The central concept in genetic counseling with such families is to estimate the probability of recurrence of unfavorable pregnancy outcomes. The main questions that consultants usually ask are: Why did this happen? What is the risk to be done again? Our cases were two families with repeated miscarriage. The pedigrees were drawn, the chromosomes of couples were studied, and estimation for recurrent risk was done. We tried to answer those two main questions and clear the results for them. Parental chromosome abnormalities were founded after karyotyping with GTG technique at 450 band resolution, revealing 46 chromosomes with balanced translocation of autosomes in one of the partner in both families. Recurrent risk was estimated as "high" for their future pregnancies in each family. Couples in which one partner is the carrier of such balanced translocation have increased risks of infertility, recurrent abortion, and delivery of chromosomally abnormal offspring. Genetic counseling of such couples, therefore, presents a unique challenge and should be considered in dealing with such families.

Indications and Outcome of Anti-phospholipid Syndrome Testing in an Obstetric Population at Sabah Women & Children Hospital, Kota Kinabalu, Sabah, Borneo Malaysia

Aim: We audited indications and outcomes of antiphospholipid syndrome (APS) screening in the pregnant population at our centre. Method: Prospective and observational. All APS test results returned were audited for validity of indication and subsequent outcome. Result: 24 of a total of 146 (16%) of requests for the antiphospholipid antibodies and lupus anticoagulant were not indicated. Two positive results returned for a total of 116 “indicated” requests (1.7%). Conclusion: There needs to be increased awareness among obstetricians on the indications for screening for antiphospholipid syndrome (APS). The prevalence of antiphospholipid syndrome with obstetric manefestations in the study population is lower than rates published in the literature.

Laparoscopic cervicoisthmic cerclage for the treatment of cervical incompetence: case reports / Cerclaje cérvico-ístmico laparoscópico en el tratamiento de la incompetencia cervical: reporte de casos

Cervical insufficiency/incompetence occurs in 0.5-1% of all pregnancies, often resulting in significant pregnancy lost. Three women with a history of second trimester miscarriages after failed transvaginal cervical cerclages were reviewed. A laparoscopic cervicoisthmic cerclage (LCC) was placed before pregnancy without any intra-operative or postoperative complications. Two patients have since delivered live babies at term by Caesarean section. This small case series supports the conclusion that LCC is a safe and cost-effective procedure in properly selected patients. Laparoscopic cervicoisthmic cerclage costs less, is less invasive, has fewer complications and should replace the traditional laparotomy technique.

La insuficiencia/incompetencia cervical ocurre en 0.5-1% de todos los embarazos, trayendo a menudo como consecuencia una pérdida significativa de embarazos. Se revisaron los casos de tres mujeres con una historia de abortos en el segundo trimestre después de cerclajes cervicales transvaginales fallidos. Un cerclaje cérvico-ístmico laparoscópico (CCL) se realizó antes del embarazo sin ninguna complicación intraoperatoria o postoperatoria. Desde entonces, dos pacientes han parido bebés vivos a término por cesárea. Esta pequeña serie de casos sustenta la conclusión de que el CCL es un procedimiento seguro y costo-efectivo en pacientes propiamente seleccionados. El cerclaje cérvico-ístmico laparoscópico cuesta menos, es menos invasivo, tiene menos complicaciones, y debe reemplazar la técnica de laparotomía tradicional.

Frecuencia de mosaicismos de baja proporción del cromosoma x en parejas con antecedente de aborto recurrente / Frequency of Low-level Mosaicism in X-Cromosome in Couples with Antecedent of Recurrent Miscarriages

El aborto recurrente se presenta entre el 1 y 7% de las parejas. Su etiología comprende factores genéticos, inmunológicos, anatómicos, hormonales, metabólicos, trombofílicos e infecciosos. Con el objetivo de establecer la frecuencia de mosaicismos de baja proporción en cromosomas sexuales, en una población de parejas con antecedente de aborto recurrente, se hizo un estudio citogenético prospectivo caso- control en 20 parejas, remitidas al Laboratorio de Biogenética del Centro Colombiano de Fertilidad y Esterilidad (CECOLFES). Se hizo valoración clínico-patológica, estudios anatómicos, hormonales, infecciosos, andrológicos y genéticos. Como técnicas citogenéticas se usaron el método convencional de bandeo GTG para el estudio de anomalías cromosómicas numéricas y estructurales y el método molecular de Hibridación in situ con Fluorescencia (FISH) para confirmar los mosaicismos en cromosomas sexuales. De acuerdo con los hallazgos paraclínicos de las parejas estudiadas, el diagnóstico mostró factores inmunológicos (75%), anatómicos (30%), hormonales (25%), masculinos (25%), infecciosos (25%), genéticos (15%) e idiopático (10%). Como resultados del estudio citogenético de las parejas, hubo un 10% de mosaicismos de baja proporción en cromosomas sexuales en dos mujeres abortadoras cuyo diagnóstico final incluyó factor genético e infeccioso y factor genético e inmune respectivamente. Sólo se es- tudió citogenéticamente el 10% de los productos de aborto de todas las parejas. Se concluye la evidencia multifactorial de la patogénesis del aborto recurrente, el subdiagnóstico del factor genético en las parejas remitidas y la necesidad de focalizar investigaciones futuras en la interpretación citogenética y asociación clínico-patológica de los mosaicismo de baja proporción en cromosomas sexuales con el aborto recurrente.

Recurrent miscarriage occurs in around 1 to 7 percent of couples. The etiology involves genetic, immunologic, anatomic, hormonal, metabolic, thrombophilic and infectious factors. With the aim of establishing the frequency of low-level mosaicism in the X-chromosome, in a population of couples with prior recurrent miscarriages, a prospective case-control cytogenetic study took place on 20 couples, at the biogenetic laboratory in CECOLFES (Colombian Center of Fertility and Sterility). Clinical pathologic evaluation, anatomic, hormonal, infectious, andrologic and genetic studies were performed. As a conventional method in cytogenetic techniques, banding GTG was used for the study of structural and numeric chromosomal abnormalities whereas the molecular method of Fluorescence In Situ Hybridization (FISH) was used to confirm the mosaicism in sexual chromosomes. According to paraclinic results from the participating couples, diagnosis showed immunologic (75%), anatomic (30%), hormonal (25%), male (25%), infectious (25%), genetic (15%) and idiophatic factors (10%). Results from the cytogenetic analysis, were 10% of low-level mosaicism in the X-chromosome in two women whose final diagnosis included genetic and infectious factors for one and genetic and immunologic factors for the other. Only 10 % of the total miscarriages from the couples were evaluated. Conclusions include aspects such as multifactorial evidence of pathogenesis in recurrent miscarriage, the sub-diagnosis of genetic factors and the need to focus future investigations on cytogenetic interpretation and the clinicalpathological association between low-level mosaicism in the X-cromosome and recurrent miscarriage.